RET NTRK1 REARRANGEMENTS IN THYROID-GLAND TUMORS OF THE PAPILLARY CARCINOMA FAMILY - CORRELATION WITH CLINICOPATHOLOGICAL FEATURES/

The papillary carcinoma family (PCF) of thyroid tumors includes a wide variety of neoplastic entities regarded as well-differentiated, poorl y differentiated, and undifferentiated papillary thyroid carcinomas. R ecent studies have established the presence of alternative oncogenic r earrangements of the RET and NTRK1 genes in a consistent fraction (les s than or equal to 50%) of papillary thyroid tumors, RET oncogenic rea rrangements are also very frequent (similar to 60%) in Chernobyl radia tion-associated papillary thyroid neoplasias, which show an increased aggressiveness in terms of pathological stage at disease onset. These observations prompted us to study the relationship between the presenc e or absence of RET and NTRK1 oncogenes and the clinicopathological fe atures (age, sex, histopathology, and pTNMC2 staging) of 76 consecutiv e, non-radiation-related tumors of the PCF. As previously reported, st atistical univariate analysis revealed a correlation between the combi nation of RET and NTRK1 (RET/NTRK1) positivity and young age of patien ts at diagnosis. In addition, a significant association was found betw een RET/NTRK1 positivity and locally advanced stage of disease at pres entation (pT(4): P < 0.015). The multivariate analysis confirmed that RET/NTRK1 activation parallels an unfavorable disease presentation, wh ich may correlate with a less favorable disease outcome. Furthermore, within the PCF, the frequency of RET/NTRK1 positivity was not influenc ed by the different neoplastic subtypes or the tumor versus degree of differentiation.